Nassau University Medical Center

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

Two hundred women were interviewed within 24-36 hours after giving birth. The patients were not examined. It was found that 56% of the patients suffered from low-back pain during pregnancy. The percentage of Caucasians was statistically higher in the back pain group. The percentage of Hispanics was statistically higher in the no pain group. Among the variables that were compared in both groups were the age, the weight gained by the mothers during pregnancy, the baby's weight, the number of previous pregnancies, number of prior children. None of the variables reached a statistically significant level. The pain group complained of pain the low-back area, which radiated in 45.5% of cases to the lower extremities. In about one-third of the patients the pain increased as the day wore on, whereas in another one-third the pain increased during the night and disturbed sleep. Standing, sitting, forward bending, lifting, and walking tended to increase the pain. Most of the patients started suffering from back pain between the fifth and seventh months of pregnancy. Several theories to explain the occurrence of backache during pregnancy are discussed.

Colitis and infection due to Clostridium difficile have been reported in patients receiving antineoplastic chemotherapy for cancer without prior antibiotic treatment. Chemotherapeutic agents can alter the normal bowel flora and cause extensive intestinal inflammatory changes, potentiating both the growth of C. difficile and its production of toxin. This review includes all 23 known reported cases of C. difficile infection associated with antineoplastic chemotherapy and examines the pathogenesis, clinical features, and management of this condition. Chemotherapy-associated C. difficile colitis has been documented in association with a variety of neoplasms. Various classes of antineoplastic agents have been incriminated, methotrexate most commonly. A spectrum of illness ranging from mild to fulminant has been reported. Symptoms, management, and outcome have appeared to be no different than for antibiotic-associated cases, but the available data are limited. Chemotherapy-associated infection with C. difficile may be underreported because it is not suspected and/or because frequent concomitant use of antibiotics masks its true incidence. C. difficile infection should be kept in mind whenever a patient undergoing antineoplastic chemotherapy develops diarrhea. Prompt, appropriate diagnostic testing and early treatment may avert morbidity and death.

CONTEXT: Many changes in health care delivery, health legislation, and the physician workforce that affect the supply and demand for endocrinology services have occurred since the first published workforce study of adult endocrinologists in 2003. OBJECTIVE: The objective of the study was to assess the current adult endocrinology workforce data and provide the first analysis of the pediatric endocrinology workforce and to project the supply of and demand for endocrinologists through 2025. DESIGN: A workforce model was developed from an analysis of proprietary and publicly available databases, consultation with a technical expert panel, and the results of an online survey of board-certified endocrinologists. PARTICIPANTS: The Endocrine Society commissioned The Lewin Group to estimate current supply and to project gaps between supply and demand for endocrinologists. A technical expert panel of senior endocrinologists provided context, clinical information, and direction. MAIN OUTCOME MEASURES: The following were measured: 1) the current adult and pediatric endocrinology workforce and the supply of and demand for endocrinologists through 2025 and 2) the number of additional entrants into the endocrinology work pool that would be required to close the gap between supply and demand. RESULTS: Currently there is a shortage of approximately 1500 adult and 100 pediatric full-time equivalent endocrinologists. The gap for adult endocrinologists will expand to 2700 without an increase in the number of fellows trained. An increase in the prevalence of diabetes mellitus further expands the demand for adult endocrinologists. The gap can be closed in 5 and 10 years by increasing the number of fellowship positions by 14.4% and 5.5% per year, respectively. The gap between supply and demand for pediatric endocrinologists will close by 2016, and thereafter an excess supply over demand will develop at the current rate of new entrants into the work force. CONCLUSIONS: There are insufficient adult endocrinologists to satisfy current and future demand. A number of proactive strategies need to be instituted to mitigate this gap.

BACKGROUND: Radiation safety is an essential component in the treatment of patients with thyroid diseases by ¹³¹I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines. METHODS: Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection [corrected] recommendations formed the basic structure of the recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines. RESULTS: The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with ¹³¹I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home. CONCLUSION: Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with ¹³¹I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with ¹³¹I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.

CONTEXT: Disorders of sex development (DSD) are clinical conditions where there is a discrepancy between the chromosomal sex and the phenotypic (gonadal or genital) sex of an individual. Such conditions can be stressful for patients and their families and have historically been difficult to diagnose, especially at the genetic level. In particular, for cases of 46,XY gonadal dysgenesis, once variants in SRY and NR5A1 have been ruled out, there are few other single gene tests available. OBJECTIVE: We used exome sequencing followed by analysis with a list of all known human DSD-associated genes to investigate the underlying genetic etiology of 46,XY DSD patients who had not previously received a genetic diagnosis. DESIGN: Samples were either submitted to the research laboratory or submitted as clinical samples to the UCLA Clinical Genomic Center. Sequencing data were filtered using a list of genes known to be involved in DSD. RESULTS: We were able to identify a likely genetic diagnosis in more than a third of cases, including 22.5% with a pathogenic finding, an additional 12.5% with likely pathogenic findings, and 15% with variants of unknown clinical significance. CONCLUSIONS: Early identification of the genetic cause of a DSD will in many cases streamline and direct the clinical management of the patient, with more focused endocrine and imaging studies and better-informed surgical decisions. Exome sequencing proved an efficient method toward such a goal in 46,XY DSD patients.

BACKGROUND: The current study was designed to examine whether a combination of three nutrients, consisting of beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of leucine, L-glutamine (Gln) and L-arginine (Arg), each of which has been previously shown to slow muscle proteolysis, could synergistically alter the course of muscle wasting in patients with established acquired immunodeficiency syndrome (AIDS). METHODS: Sixty-eight human immunodeficiency virus (HIV)-infected patients with a documented weight loss of at least 5% in the previous 3 months were recruited from the HIV clinic at Nassau County Medical Center. The subjects were randomly assigned in a double-blind fashion to receive either placebo containing maltodextrin or the nutrient mixture (HMB/Arg/Gln) containing 3 g HMB, 14 g L-glutamine, and 14 g L-arginine given in two divided doses daily for 8 weeks. Body weights (BW) were recorded weekly and lean body mass (LBM) and fat mass (FM) were measured by air displacement plethysmography and by a single computerized tomography (CT) slice through the thigh at 0, 4, and 8 weeks. RESULTS: Forty-three subjects completed the 8-week protocol, (placebo, n = 21; HMB/Arg/Gln, n = 22). At 8 weeks, the subjects consuming the HMB/Arg/Gln mixture gained 3.0 +/- 0.5 kg of BW while those supplemented with the placebo gained 0.37 +/- 0.84 kg (p = .009). The BW gain in the HMB/Arg/Gln-treated subjects was predominantly LBM (2.55 +/- 0.75 kg) compared with the placebo-supplemented subjects who lost lean mass (-0.70 +/- 0.69 kg, p = .003). No significant change in FM gain was observed (0.43 +/- 0.83 kg for the group receiving HMB/Arg/Gln and 1.07 +/- 0.64 kg for the group receiving the placebo, p > .20). Similar percentage changes in muscle mass and fat mass were observed with CT scans. Immune status was also improved as evident by an increase in CD3 and CD8 cells and a decrease in the HIV viral load with HMB/Arg/Gln supplementation. CONCLUSIONS: The data indicate that the HMB/Arg/Gln mixture can markedly alter the course of lean tissue loss in patients with AIDS-associated wasting.

Traumatic brain injury (TBI) occurs when a blow or jolt to the head or a penetrating injury results in damage to the brain. It is the most frequent cause of hospitalization in young people with a higher prevalence in men. TBI is the leading cause of disability and mortality between the ages 1 and 45. TBI can be caused either by the direct result of trauma or due to a complication of the primary injury. The most common etiological factors for TBI are falls, road traffic accidents, violent physical assaults, and injuries associated with athletic activities. Following TBI, significant neurologic complications may occur which include seizures, dementia, Alzheimer's disease, and cranial nerve injuries. In addition, people may suffer from various psychiatric complications such as depression, posttraumatic stress disorder, generalized anxiety disorder, obsessive-compulsive disorder, and other cognitive and behavioral sequel that might significantly increase the comorbidity of the victims. Considering all of the above complications, TBI is one of the significant public health burdens. Literature has shown that only about 25% of people achieve long-term functional independence following TBI. In this paper, we focused not only on the epidemiology but also the etiology, complications following TBI and understanding their underlying pathogenesis. Further, we focused on analyzing the options to improve the treatment and rehabilitation following TBI in future.

Abstract One hundred and fifteen consecutive patients with documented active tuberculosis were skin-tested with three different tuberculin preparations, each of which reportedly contained 5 Tuberculin Units (5 TU) of purified protein derivative (PPD). A surprising lack of uniformity was demonstrated. Commercial antigen (PPD-PD) was associated with negative (0 to 4 mm) reactions in 49 per cent and doubtful (5 to 9 mm) reactions in 10 per cent of these patients. Purified protein derivative standard (PPD-S) gave 34 per cent negative and 3 per cent doubtful reactions. PPD stabilized with Tween-80 resulted in negative reactions in 17 per cent and doubtful reactions in 2 per cent of patients. A major factor in these false and nonpositive results appears to be loss of potency of the antigen through adsorption. Nonstabilized preparations are probably delivering less antigen than stated by the manufacturer, and this point is of great importance at low doses (i.e., 5 TU).

OBJECTIVES: To empirically define a "delay" for hip fracture surgery based on clinical outcomes, and to identify patient demographics and hospital factors contributing to surgical delay. DESIGN: Retrospective database analysis. SETTING: Hospital discharge data. PATIENTS/PARTICIPANTS: A total of 2,121,215 patients undergoing surgical repair of hip fracture in the National Inpatient Sample between 2000 and 2009. INTERVENTION: Internal fixation or partial/total hip replacement. MAIN OUTCOME MEASUREMENTS: Logistic regressions were performed to assess the effect of surgical timing on in-hospital complication and mortality rates, controlling for patient characteristics and hospital attributes. Subsequent regressions were performed to analyze which patient characteristics (age, gender, race, comorbidity burden, insurance status, and day of admission) and hospital factors (size, teaching status, and region) independently contributed to the likelihood of surgical delay. RESULTS: Compared to same-day surgery, each additional day of delay was associated with a significantly higher overall complication rate. However, next-day surgery was not associated with an increased risk of in-hospital mortality. Surgery 2 calendar days (odds ratio: 1.13) and 3+ days (odds ratio: 1.33) after admission was associated with higher mortality rates. Based on these findings, "delay" was defined as surgery performed 2 or more days after admission. Significant factors related to surgical delay included comorbidity score, race, insurance status, hospital region, and day of admission. CONCLUSIONS: Surgical delay in hip fracture care contributes to patient morbidity and mortality. A variety of patient and hospital characteristics seem to contribute to surgical delay and point to important health care disparities. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Cardiovascular diseases exert a significant burden on the healthcare system worldwide. This narrative literature review discusses the role of artificial intelligence (AI) in the field of cardiology. AI has the potential to assist healthcare professionals in several ways, such as diagnosing pathologies, guiding treatments, and monitoring patients, which can lead to improved patient outcomes and a more efficient healthcare system. Moreover, clinical decision support systems in cardiology have improved significantly over the past decade. The addition of AI to these clinical decision support systems can improve patient outcomes by processing large amounts of data, identifying subtle associations, and providing a timely, evidence-based recommendation to healthcare professionals. Lastly, the application of AI allows for personalized care by utilizing predictive models and generating patient-specific treatment plans. However, there are several challenges associated with the use of AI in healthcare. The application of AI in healthcare comes with significant cost and ethical considerations. Despite these challenges, AI will be an integral part of healthcare delivery in the near future, leading to personalized patient care, improved physician efficiency, and anticipated better outcomes.

Mortality remains very high among septic patients despite the advanced treatments rendered in intensive care units. The development of septic shock is multifactorial. Tissue damage and organ dysfunction may be caused not only by the microorganisms but also by the inflammatory mediators released in response to the infection. Cytokines (tumor necrosis factor, interleukin-1, interleukin-6, interleukin-8, high-mobility group box-1 protein, macrophage migratory inhibitory factor) and noncytokines (nitric oxide, platelet-activating factor, complements, and eicosonoids) may inflict tissue injury and contribute to multiple organ dysfunction and cell death (or apoptosis). Gram-negative bacteria are the most common organisms identified in septic patients. The pathological effects of gram-negative bacteria are conveyed through lipopolysaccharide derived from the bacterial cell membrane. Lipopolysaccharide activates the nuclear factor kappa B, which triggers the release of inflammatory mediators. Protein components from gram-positive bacteria, fungi, or viruses may evoke the activation of nuclear factor kappa B in a similar fashion as lipopolysaccharide. Endogenous anti-inflammatory mediators are released in response to the infection and act to control the overwhelming systemic inflammatory response. The fragile balance between negative and positive feedback on the inflammatory mediators is the key factor that modulates the cellular damage and influences the clinical outcome.

The Mahalanobis–Taguchi system (MTS) is a relatively new collection of methods proposed for diagnosis and forecasting using multivariate data. The primary proponent of the MTS is Genichi Taguchi, who is very well known for his controversial ideas and methods for using designed experiments. The MTS results in a Mahalanobis distance scale used to measure the level of abnormality of “abnormal” items compared to a group of “normal” items. First, it must be demonstrated that a Mahalanobis distance measure based on all available variables on the items is able to separate the abnormal items from the normal items. If this is the case, then orthogonal arrays and signal-to-noise ratios are used to select an “optimal” combination of variables for calculating the Mahalanobis distances. Optimality is defined in terms of the ability of the Mahalanobis distance scale to match a prespecified or estimated scale that measures the severity of the abnormalities. In this expository article, we review the methods of the MTS and use a case study based on medical data to illustrate them. We identify some conceptual, operational, and technical issues with the MTS that lead us to advise against its use.

LEARNING OBJECTIVES: After reviewing this article, the participant should be able to: 1. Understand the most modern indications and technique for neurotization, including masseter-to-facial nerve transfer (fifth-to-seventh cranial nerve transfer). 2. Contrast the advantages and limitations associated with contiguous muscle transfers and free-muscle transfers for facial reanimation. 3. Understand the indications for a two-stage and one-stage free gracilis muscle transfer for facial reanimation. 4. Apply nonsurgical adjuvant treatments for acute facial nerve paralysis. SUMMARY: Facial expression is a complex neuromotor and psychomotor process that is disrupted in patients with facial paralysis breaking the link between emotion and physical expression. Contemporary reconstructive options are being implemented in patients with facial paralysis. While static procedures provide facial symmetry at rest, true 'facial reanimation' requires restoration of facial movement. Contemporary treatment options include neurotization procedures (a new motor nerve is used to restore innervation to a viable muscle), contiguous regional muscle transfer (most commonly temporalis muscle transfer), microsurgical free muscle transfer, and nonsurgical adjuvants used to balance facial symmetry. Each approach has advantages and disadvantages along with ongoing controversies and should be individualized for each patient. Treatments for patients with facial paralysis continue to evolve in order to restore the complex psychomotor process of facial expression.

OBJECTIVE: Clostridium difficile gastrointestinal disease is an important nosocomial infection and is associated with recent antibiotic use. This study evaluated C. difficile-associated diarrhea (CDAD) over a 2-yr period. METHODS: All 60 patients with C. difficile enterotoxin in their stools, and diarrhea, were retrospectively analyzed at a 615-bed teaching hospital. Institution antibiotic usage and discharge medical diagnoses were correlated with the study patients. RESULTS: Thirty-eight study patients (53%) had major or extreme admitting symptoms. Only four (7%) had no co-morbid illness. The incidence of CDAD increased significantly (p < 0.05) after 4 wk of hospitalization. No demographic or temporal clustering was discovered. Leukocytosis (60%), leftward polymorphonuclear shift (47%), dehydration (30%), weight loss (23%), and oliguria (12%) were the major clinical findings. Among these subject 51 (85%) had been on ceftriaxone and/or ceftazidime in the preceding 6 wk; ceftriaxone/ceftazidime was highly significantly associated (p < 0.01) with more cases than expected by usage alone. No patient on ticarcillin/clavulanate developed CDAD, although it was the most commonly used antibiotic (p < 0.00001). Higher mortality was associated with older debilitated nursing home residents. CONCLUSIONS: Third-generation cephalosporin use correlated with the development of CDAD; ticarcillin/clavulanate usage did not. Morbidity and mortality associated with CDAD is significant, is worse in debilitated older nursing home patients, and is more likely to occur in hospitalizations lasting longer than 4 wk.

This is a book review of The Health Physics and Radiological Health Handbook. The author discusses the highlights of this near-encyclopedic compendium on Health Physics. He stresses that in spite of an abundance of typographical errors, that it is a very good and complete reference tool.

An attempt was made to determine the effect of pregnancy on the abdominal muscles and to correlate changes in abdominal muscles strength with low-back pain during pregnancy. The study included 328 women. Group A consisted of 164 pregnant women; group B consisted of 164 non-pregnant women. The race, age, height, weight, parity, profession, time devoted to physical fitness per week, abdominal length, and relation between the abdominal length to height were recorded. A detailed history relating to backache prior to and during pregnancy was obtained. Each woman was asked to perform a single sit-up. The results of the study indicate that about 10% of pregnant women develop severe low-back pain that interferes with daily life activities. About 49% of the non-pregnant women complained of LBP. The pain did not interfere with activities of daily living. During pregnancy, due to overstretching of the abdominal muscles, the ability to perform a sit-up is significantly decreased. Whereas all non-pregnant women could perform a sit-up, 16.6% of pregnant women could not perform a single sit-up. There was no statistically significant correlation between the sit-up performance and backache. It may be concluded that during pregnancy the abdominal muscles become insufficient.

To investigate the incidence, culture results, treatment, and visual outcomes of infectious keratitis after laser in situ keratomileusis (LASIK) worldwide, the Cornea Clinical Committee of the American Society of Cataract and Refractive Surgery (ASCRS) contacted 8600 United States and international ASCRS members by e-mail and asked them to respond to a questionnaire about post-LASIK infectious keratitis. One hundred sixteen infections were reported by 56 LASIK surgeons who had performed an estimated 338 550 procedures. Seventy-six cases presented in the first week after surgery, 7 during the second week, 17 between the second and fourth weeks, and 16 after 1 month. Forty-seven cases were not diagnosed on initial presentation. The most common organisms cultured were atypical mycobacteria and staphylococci. Empiric therapy is not recommended as most of the organisms are opportunistic and not responsive to conventional therapy. Flap elevation and culturing should be performed when post-LASIK infectious keratitis is suspected.

BACKGROUND: Non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. RESULTS: We performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients' overall survival. CONCLUSIONS: The primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific.

There is evidence that mature dendritic cells (DCs) present in the rheumatoid arthritis (RA) joint mediate immunopathology in RA. In this study, we indicate that early myeloid progenitors for DCs and DC growth factors existing in RA synovial fluid (SF) are also likely participants in the RA disease process. A fraction of cells lacking markers associated with mature DCs or DC precursors and enriched in CD34(negative) myeloid progenitors was isolated from RA SF. These cells proliferated extensively when cultured in vitro with cytokines that promote the growth of myeloid DCs (GM-CSF/TNF/stem cell factor/IL-4) and, to a lesser degree, when cultured with monocyte/granulocyte-restricted growth factors (M-CSF/GM-CSF). Mature DCs derived from RA SF progenitors with CD14-DC cytokines known to be prevalent in the inflamed RA joint (GM-CSF/TNF/stem cell factor/IL-13) were potent stimulators of allogeneic T cells and inflammatory-type Th1 responses and included CD14-DC subtypes. Cell-free RA SF facilitated DC maturation from myeloid progenitors, providing direct evidence that the inflamed RA joint environment instructs DC growth. Enhanced development of CD14-derived DCs was correlated with the presence of soluble TNFR (p55), raising the possibility that soluble TNFR also regulate CD14-derived DC growth in vivo. SF from patients with osteoarthritis contained neither myeloid DC progenitors nor DC growth factors. The existence of DC progenitors and myeloid DC growth factors in RA SF supports the concept that RA SF may be a reservoir for joint-associated DCs and reveals a compelling mechanism for the amplification and perpetuation of DC-driven responses in the RA joint, including inflammatory-type Th1 responses.